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MHC associations with clinical and autoantibody manifestations in European SLE

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the developmen...

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Autores principales: Morris, DL, Fernando, MMA, Taylor, KE, Chung, SA, Nititham, J, Alarcón-Riquelme, ME, Barcellos, LF, Behrens, TW, Cotsapas, C, Gaffney, PM, Graham, RR, Pons-Estel, BA, Gregersen, PK, Harley, JB, Hauser, SL, Hom, G, Langefeld, CD, Noble, JA, Rioux, JD, Seldin, MF, Vyse, TJ, Criswell, LA
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102853/
https://www.ncbi.nlm.nih.gov/pubmed/24598797
http://dx.doi.org/10.1038/gene.2014.6
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author Morris, DL
Fernando, MMA
Taylor, KE
Chung, SA
Nititham, J
Alarcón-Riquelme, ME
Barcellos, LF
Behrens, TW
Cotsapas, C
Gaffney, PM
Graham, RR
Pons-Estel, BA
Gregersen, PK
Harley, JB
Hauser, SL
Hom, G
Langefeld, CD
Noble, JA
Rioux, JD
Seldin, MF
Vyse, TJ
Criswell, LA
author_facet Morris, DL
Fernando, MMA
Taylor, KE
Chung, SA
Nititham, J
Alarcón-Riquelme, ME
Barcellos, LF
Behrens, TW
Cotsapas, C
Gaffney, PM
Graham, RR
Pons-Estel, BA
Gregersen, PK
Harley, JB
Hauser, SL
Hom, G
Langefeld, CD
Noble, JA
Rioux, JD
Seldin, MF
Vyse, TJ
Criswell, LA
author_sort Morris, DL
collection PubMed
description Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.
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spelling pubmed-41028532014-07-18 MHC associations with clinical and autoantibody manifestations in European SLE Morris, DL Fernando, MMA Taylor, KE Chung, SA Nititham, J Alarcón-Riquelme, ME Barcellos, LF Behrens, TW Cotsapas, C Gaffney, PM Graham, RR Pons-Estel, BA Gregersen, PK Harley, JB Hauser, SL Hom, G Langefeld, CD Noble, JA Rioux, JD Seldin, MF Vyse, TJ Criswell, LA Genes Immun Article Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies. 2014-03-06 2014-04 /pmc/articles/PMC4102853/ /pubmed/24598797 http://dx.doi.org/10.1038/gene.2014.6 Text en © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Morris, DL
Fernando, MMA
Taylor, KE
Chung, SA
Nititham, J
Alarcón-Riquelme, ME
Barcellos, LF
Behrens, TW
Cotsapas, C
Gaffney, PM
Graham, RR
Pons-Estel, BA
Gregersen, PK
Harley, JB
Hauser, SL
Hom, G
Langefeld, CD
Noble, JA
Rioux, JD
Seldin, MF
Vyse, TJ
Criswell, LA
MHC associations with clinical and autoantibody manifestations in European SLE
title MHC associations with clinical and autoantibody manifestations in European SLE
title_full MHC associations with clinical and autoantibody manifestations in European SLE
title_fullStr MHC associations with clinical and autoantibody manifestations in European SLE
title_full_unstemmed MHC associations with clinical and autoantibody manifestations in European SLE
title_short MHC associations with clinical and autoantibody manifestations in European SLE
title_sort mhc associations with clinical and autoantibody manifestations in european sle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102853/
https://www.ncbi.nlm.nih.gov/pubmed/24598797
http://dx.doi.org/10.1038/gene.2014.6
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